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Notch2 signal is required for the maintenance of canine hemangiosarcoma cancer stem cell-like cells

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Title: Notch2 signal is required for the maintenance of canine hemangiosarcoma cancer stem cell-like cells
Authors: Aoshima, Keisuke Browse this author
Fukui, Yuki Browse this author
Gulay, Kevin Christian Montecillo Browse this author
Erdemsurakh, Ochbayar Browse this author
Morita, Atsuya Browse this author
Kobayashi, Atsushi Browse this author
Kimura, Takashi Browse this author →KAKEN DB
Keywords: Cancer stem cell-like cells
Hemangiosarcoma
Notch2
Oncology
Tumor Biology
Issue Date: 3-Oct-2018
Publisher: BioMed Central
Journal Title: BMC veterinary research
Volume: 14
Start Page: 301
Publisher DOI: 10.1186/s12917-018-1624-8
Abstract: Background: Hemangiosarcoma (HSA) is a malignant tumor derived from endothelial cells which usually shows poor prognosis due to its high invasiveness, metastatic rate and severe hemorrhage from tumor ruptures. Since the pathogenesis of HSA is not yet complete, further understanding of its molecular basis is required. Results: Here, we identified Notch2 signal as a key factor in maintaining canine HSA cancer stem cell (CSC)-like cells. We first cultured HSA cell lines in adherent serum-free condition and confirmed their CSC-like characteristics. Notch signal was upregulated in the CSC-like cells and Notch signal inhibition by a.-secretase inhibitor significantly repressed their growth. Notch2, a Notch receptor, was highly expressed in the CSC-like cells. Constitutive activation of Notch2 increased clonogenicity and number of cells which were able to survive in serum-free condition. In contrast, inhibition of Notch2 activity showed opposite effects. These results suggest that Notch2 is an important factor for maintaining HSA CSC-like cells. Neoplastic cells in clinical cases also express Notch2 higher than endothelial cells in the normal blood vessels in the same slides. Conclusion: This study provides foundation for further stem cell research in HSA and can provide a way to develop effective treatments to CSCs of endothelial tumors.
Rights: https://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/71994
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 青島 圭佑

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